PROJECT SUMMARY The purpose of the Lipidomics Shared Resource Core (LSR Core) in the PPG is to provide intellectual and physical resources (particularly state-of-the-art mass spectrometry analysis of sphingolipids and synthetic molecular tools to study lipids) to enhance our understanding of the role of bioactive lipids in cancer biology with the goal to discover future drugs. The diversity of bioactive lipids and their interconnected metabolism generates a network of pathways regulating intra- and inter-cellular signaling and function. Dysfunctions in these pathways contribute to the pathobiology of cancer progression and metastasis. These considerations have necessitated the development of lipid chemistry and analysis. The LSR Core was created based on unique expertise of the key personnel in lipid chemistry, analysis, and metabolism. It has evolved into a key Core for the program project grant (PPG) entitled Sphingolipids in Cancer Biology and Therapeutics, and was used by all participating investigators. Furthermore, this Core has developed into an institutional, national, and international resource in the emerging fields of lipidomics and lipid chemical biology. Core services include: 1) providing qualitative and quantitative analysis of lipid components from different biological materials (cells, tissue, and biological fluids), primarily employing high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technology-the Core currently provides quantitative analysis of more than 300 distinct lipid molecular species at a basic metabolomic level; 2) developing and providing synthetic molecular tools to study lipid metabolism (e.g., functionalized and fluorescent ceramides, site-specific radioactive sphingolipids, 17C-sphingolipids) and diversified synthetic lipids and analogs for cellular, in vitro, and in vivo studies (e.g., organelle-targeted sphingolipids and organelle-targeted inhibitors of sphingolipid metabolizing enzymes); and 3) assisting PPG investigators in experimental design, selection of lipids of interest, and interpretation of analytical results. The LSR Core has been instrumental to the success of the PPG investigators over the past 10 years by providing them with unique capabilities and critical results that should continue to contribute for the successful progress of this PPG renewal.